A number of radiolabelled haloaromatic compounds have found application in nuclear medicine. For example, meta-iodobenzylguanidine (“MIBG”), when radiolabelled with the iodine atom, is used in nuclear medicine as either an imaging agent for diagnosis, or as a therapeutic agent for neural crest tumors such as neuroblastoma. When labelled with the shorter-lived iodine-123, [123I]MIBG provides diagnostic cardiac images as well as images of tumors. The longer-lived [131I]MIBG is used at much higher radiation and chemical doses for the treatment of tumors.
By far the most common method of producing either [123I]MIBG or [131I]MIBG is by a Cu+ catalyzed isotopic exchange process which commences with 1-2 mg of MIBG and the desired amount of radioiodide. Because isotopic exchange is an equilibrium process, the product obtained by this process necessarily contains a significant amount of carrier MIBG. Considerable effort1 has been placed towards developing a convenient procedure that proceeds in near quantitative radiochemical yields. However, this method has the drawback of producing [131I]MIBG of low specific activity resulting in chemical doses of 1-5 mg when therapeutic samples are prepared. Doses of this magnitude carry potential hypertensive side effects.
Accordingly, routes to no-carrier-added [131I]MIBG have been developed which could reduce the chemical dose of MIBG by about a factor of 100. Precursors to no-carrier-added [131I]MIBG, such as 3-tributylstannylbenzylamine2, 3-trimethylsilylbenzylguanidine2, and 3-trimethylstannylguanidinium3, have not found widespread application. These compounds have a short shelf life, and must be stored in a freezer shielded from light.
U.S. Pat. No. 5,565,185 discloses a no-carrier-added process of radiolabelling MIBG by halodestannylation. However, the process is disadvantageous in that a number of impurities remain in solution with the radiolabelled MIBG. In particular, toxic tin by-products remain in solution and must be separated before the radiolabelled MIBG is ready for use.
Accordingly, there is a need for a process for no-carrier-added synthesis of radiolabelled haloaromatic compounds, which can be easily and practically separated from possibly toxic impurities.